Biofilms are structured communities of microorganisms that can be firmly attached to a surface and enmeshed in a self-produced three-dimensional (3D) extracellular matrix. Biofilms can form on living or non-living surfaces and can exist in natural and industrial settings. For example, biofilms can contaminate man-made aquatic systems such as cooling towers, pools and spas. In the industrial setting, biofilms can develop on the interiors of pipes that can lead to clogs and corrosion. Biofilms can also be formed within implanted medical tubing and medical devices as well as within the human body (mucosal surfaces), which can lead to infections in patients. Similarly, biofilms can develop within the oral cavity and result in oral diseases such as dental caries. The extracellular matrices of such biofilms contain polymeric substances, such as exopolysaccharides (EPS). The matrix produced by microorganisms can provide an essential scaffold for biofilm assembly. Additionally, it can promote microbial adhesion and cohesion while hindering diffusion, thereby making biofilms extremely difficult to treat or remove from surfaces.
In the oral cavity context, EPS, which form the core of the matrix, are the prime building blocks of cariogenic, i.e., caries-producing, biofilms (also known as dental plaques). This EPS-rich extracellular matrix promote the formation of highly cohesive and adherent biofilms as well as hinder diffusion that helps create highly acidic microenvironments within the biofilm. Such high acidity can enhance the survival and growth of cariogenic flora, and can further induce the production of the polymeric extracellular matrix, thereby ensuring pathogenic biofilm accretion while promoting acid-dissolution of the adjacent tooth enamel. This extracellular matrix also contributes to the difficulty in the elimination of microbial biofilms within the oral cavity and human body, as well as on biomaterials, e.g., implants and medical devices, by antibodies, antibiotics and immune cells, which are unable to penetrate the dense extracellular matrix to kill the embedded microorganisms. Furthermore, the acidic pH of the EPS-rich extracellular matrix can reduce efficacy of some antibiotics.
Certain approaches for controlling cariogenic biofilms are restricted to standard bactericidal agents, such as chlorhexidine (CHX), rather than targeting matrix disruption. Although capable of killing planktonic Streptococcus mutans, CHX can be less effective against biofilms and is not suitable for daily therapeutic use due to adverse effects such as calculus formation and tooth staining. In addition, chemical and biological agents can have some disadvantages, such as discoloration of teeth or tongue, desquamation and soreness of oral mucosa, objectionable taste, toxicity and can also cause an imbalance of the complex oral flora.
Certain antimicrobial nanoparticles have been explored as potential approaches to disrupt oral biofilms. However, many have limitations similar to those seen with CHX. Metal nanoparticles, such as silver and copper nanoparticles, have shown broad antibacterial activity. However, these agents do not target the matrix and may not work well under acidic microenvironments, resulting in limited anti-biofilm efficacy. The development of effective therapies to control oral biofilms is also affected by the lack of retention and bioactivity of topically introduced agents in the mouth. Therefore, there is a need in the art for compositions that can effectively treat biofilms in general by simultaneously degrading the matrix and killing embedded bacteria, including, but not limited to those that can appear in the oral cavity.